In recent years, disease patterns have changed from acute infectious diseases to chronic inflammatory diseases because of a change in life style. Inflammation is a defense mechanism occurring in the body in response to external toxic substances entering the body. Acute inflammation is triggered by short-term infection of environmental bacteria, fungi, etc., and chronic inflammation is triggered when causative agents such as microorganisms, allergens, etc. that exist in the environment are continuously absorbed into the body. Recently, the importance of infectious causes for the occurrence of chronic inflammatory diseases that have been recognized to be triggered by noninfectious causes is being emphasized. As, representatively, helicobacter bacteria that have been known to co-exist in the stomach have been identified as a critical causative agent of gastritis, gastric cancer, etc., bacteria and substances derived from the bacteria, which are known to co-exist in the environment, have recently attracted attention as causative agents of cancer triggered by chronic inflammatory diseases and complications of chronic inflammation.
Atopic dermatitis is a type of dermal disease that is most frequently found in early-infancy and childhood, and the first signal of atopic march progressing to asthma or allergic rhinitis. In addition, atopic dermatitis is a chronic inflammatory disease characterized by chronic itching and repeated inflammation of the skin and thus physically and mentally affecting not only the patient himself but also the quality of life in the family. In recent years, the increase in global prevalence of the atopic dermatitis is being followed by an increasing attention thereto. In Korea, according to the International Study of Allergy and Asthma in Childhood (ISAAC) survey conducted by the Korean Pediatric Allergy Respiratory Society, for atopic dermatitis until now, compared to 1995, prevalence increased both at the ages ranging from 6 to 12 in 2000 (15.3% in 1995 and 17.0% in 2000) and at the ages ranging from 12 to 15 (7.2% in 1995 and 9.2% in 2000), and for atopic dermatitis in the last 12 months, prevalence increased both at the age ranging from 6 to 12 in 2000 (7.3% in 1995 and 10.7% in 2000), and at the ages ranging from 12 to 15 (3.9% in 1995 and 6.1% in 2000). An allergic disease such as atopic dermatitis is triggered by combined interaction between a genetic factor and an environmental factor, and the recent growth trend is insufficient to be explained only by the genetic factor. Although differences in incidence of allergic diseases depending on a country reflects differences among ethnic groups, that is, the significance of genetic factors, the same result as shown by a surge of allergic diseases in the former East German region after reunification indicates that environmental factors are also significant. Such a surge of allergic diseases is involved in westernized life, and there may be three possible causes: first, an increase in exposure to house dust mites because of generally spending more time indoors, secondly, exposure to a wide range of microorganisms due to environmental hygiene and use of antibiotics, and thirdly, westernized eating habits.
Atopic dermatitis patients frequently have dermal infection caused by functional disorder of a skin barrier, or immune dysfunction. Particularly, bacterial infections by Staphylococcus, viral infections by herpes simplex viruses, and fungal infections are common. Among these, Staphylococcus aureus is detected in 90% of patients with atopic dermatitis and is also detected in skin lesions without obvious infection symptoms, and the toxin of Staphylococcus aureus serves as a superantigen that increases allergic immune responses, which is known to exacerbate skin itching and lesions.
The prognosis of atopic dermatitis varies depending on a patient's skin condition, stimulation factor, accompanying allergic disease, and bacterial infection. Generally, atopic dermatitis tends to improve with an increasing age, while symptoms are severe at the young age and chronic lesions persist. However, some reports show that about 40% of patients have improved symptoms at the age of around 5, and the reason for this improvement is controversial. The most representative method for treating atopic dermatitis when exacerbated due to various reasons includes elimination of the causative agents and simultaneous application of topical and systemic steroids or topical immunosuppressants as well as proper use of moisturizers. However, recent studies suggest that, in addition to these factors, lactic acid bacteria or a culture thereof may be used to lower the severity of atopic dermatitis.
Asthma and chronic obstructive pulmonary disease (COPD) are diseases characterized by airway obstruction due to chronic airway inflammation, wherein the asthma is characterized by reversible airway obstruction, and the COPD is characterized by irreversible airway obstruction. A hypersensitivity reaction to allergens derived from house dust mites as a causative factor of asthma is known to be important in the pathogenesis of eosinophilic asthma, and in recent years, research has been focused on the importance of bacteria-derived substances for neutrophilic inflammation, which is a characteristic pathological feature of severe asthma or COPD. Particularly, the finding that extracellular vesicles derived from pathogenic bacteria present in indoor dust are important in the onset of asthma and COPD has been reported. In addition, it has been reported that bacteria and substances derived from the bacteria co-existing in the nasal cavity play an important role in the pathogenesis of chronic rhinosinusitis, and the reduction of the diversity of bacterial flora in the nasal cavity and the increase in specific pathogens, particularly, Staphylococci, are important in the onset of chronic rhinosinusitis.
Bacteria secrete bilayer-structured lipoproteins, that is, extracellular vesicles (EVs) frequently called nanovesicles into an extracellular environment. Gram-negative bacteria-derived extracellular vesicles, or outer membrane vesicles (OMVs) contain a toxic protein and bacterial DNA and RNA as well as lipopolysaccharides, and gram-positive bacteria-derived extracellular vesicles also contain bacterial cell wall ingredients, such as peptidoglycan and lipoteichoic acid as well as a toxic protein and nucleic acid. In recent years, it has been reported that EVs secreted from the representative gram-positive bacteria Staphylococcus aureus are important causative agents of atopic dermatitis, chronic rhinosinusitis, neutrophilic asthma and COPD, and it has been reported that large amounts of EVs derived from pathogenic gram-negative bacteria such as Pseudomonas aeruginosa and Acinetobacter bacumannii are present in indoor dust, and are important causative agents of asthma, COPD, and lung cancer when inhaled.
Meanwhile, metagenomics also called environmental genomics may be analysis of metagenome materials obtained from environmental samples. Recently, the bacterial composition of human microbial flora can be cataloged by a method based on a 16S ribosome RNA (16S rRNA) base sequence, and 16S rRNA is sequenced using the 454FLX titanium platform. In the meantime, while research has been conducted on metagenomes analyzed from patient samples, it was not known that bacteria-derived EVs are present in serum or urine, and therefore metagenomic analysis was not conducted on bacteria-derived EVs isolated from serum or urine. In addition, on the basis of results of metagenomic analysis using DNA of EVs isolated from patients' sera or urine, there is no case that bacteria-derived EVs are used to prevent or treat an inflammatory disease such as atopic dermatitis, asthma, COPD, chronic rhinitis, chronic rhinosinusitis, and sepsis.